Currently in Australia asthma prevalence is high compared with other countries, affecting 10%–12% of adults and 14%–16% of children. This project will determine the contribution of mast cells to the altered function of airway smooth muscle cells and identify how non asthmatic airway smooth muscle inhibits mast cell localisation to it. The findings will provide new targets for asthma therapies and a pathway for prevention strategies, which up until now have been unsuccessful.
Increased Airway Smooth Muscle Mass As An Independent Determinant Of Asthma Pathogenesis And Severity
Funder
National Health and Medical Research Council
Funding Amount
$409,966.00
Summary
Asthma is a major health burden to the community. The most common form of the disease is allergic asthma and it is thought that allergic inflammation drives associated airway abnormalities including increased airway smooth muscle (ASM) mass. This study tests a new hypothesis that airway abnormalities and allergy have separate origins but combine to produce allergic asthma, and it’s the individuals with the greatest amount of ASM who develop clinically severe asthma.
Heterogeneity Of Airway Smooth Muscle Remodelling In Asthma
Funder
National Health and Medical Research Council
Funding Amount
$623,078.00
Summary
Increased smooth muscle in the airways causes excessive narrowing and asthma symptoms. The distribution of the increased muscle in the lung varies between people with asthma and may determine how severe the asthma is and what treatments are best. This project will use tissues from many cases of asthma to map this distribution and will use laser scanning in the airways to develop a test to safely examine the smooth muscle in living people, in order to better treat or prevent asthma.
Targeted Corrective Gene Conversion (TCGC): Application In DMD Mutations And Delivery To Dystrophic (mdx) Muscle
Funder
National Health and Medical Research Council
Funding Amount
$496,500.00
Summary
The muscular dystrophies are inherited diseases that lead to muscle wastage and severe disabilities. The most severe forms result in the early death of newborns, but a large number are diagnosed in children showing early mild symptoms and progress steadily to severe disabling forms in the juvenile and young adult. Perhaps the most devastating of these dystrophies is Duchenne Muscular Dystrophy (DMD). This condition affects 1 in 3,300 boys, who show symptoms at around 5 years of age until wheelch ....The muscular dystrophies are inherited diseases that lead to muscle wastage and severe disabilities. The most severe forms result in the early death of newborns, but a large number are diagnosed in children showing early mild symptoms and progress steadily to severe disabling forms in the juvenile and young adult. Perhaps the most devastating of these dystrophies is Duchenne Muscular Dystrophy (DMD). This condition affects 1 in 3,300 boys, who show symptoms at around 5 years of age until wheelchair confinement by early teens. DMD boys undergo major clinical and surgical treatments which at present only provide small but significant improvements to their lives. The median age at death for Duchenne boys is 22 years. The cause of DMD has been known for almost 2 decades and is a defect in just a single component of muscle, Dystrophin which is produced by muscle cells. In general, boys with DMD possess Dystrophin which is missing an important part that prevents the breakdown of muscles during activity. As a consequence, all the muscles in DMD boys slowly break down over their lifetime until they die because the muscle which helps in drawing breath (Diaphragm) is no longer capable of helping them to breathe. The muscle component Dystrophin is produced by a gene (the dys gene) and the defect of Dystrophin is caused by a defect in the dys gene. If the dys gene defect was able to be corrected in boys with DMD, their Dystrophin may also be corrected and the breakdown of their muscle prevented. We have been able to correct the dys gene in muscle cells from a mouse with DMD. We wish to improve this technology and allow muscle to be corrected with genetically corrected fibres to form a basis for treatment of human DMD. In this way we hope to significantly improve and lengthen these boys' lives and even lead to a cure for DMD and other genetic muscle diseaseRead moreRead less
Airway Extracellular Matrix And Smooth Muscle In Chronic Obstructive Pulmonary Disease (COPD)
Funder
National Health and Medical Research Council
Funding Amount
$828,849.00
Summary
In asthma the layer of airway smooth muscle is thicker, due to more muscle cells. Airway narrowing is excessive but reversible. In chronic obstructive pulmonary disease (due mainly to smoking) the layer of airway smooth muscle is also thicker but the airways cannot be induced to open, or close. Our data suggest that this fixed airway narrowing is likely to be due to an excess of matrix between cells rather than muscle. This project will comprehensively test this new finding.
The breathing difficulty experienced by asthmatics occurs because of excessive narrowing in the bronchial tubes or airways. These airways are normally held open by the pressures in the chest during breathing. It is possible that the excessive airway narrowing in asthma occurs because these pressures are no longer effective. This may be due to changes in the airway stiffness which occurs during asthma. The project will involve experts Canada and Australia who have developed new techniques which a ....The breathing difficulty experienced by asthmatics occurs because of excessive narrowing in the bronchial tubes or airways. These airways are normally held open by the pressures in the chest during breathing. It is possible that the excessive airway narrowing in asthma occurs because these pressures are no longer effective. This may be due to changes in the airway stiffness which occurs during asthma. The project will involve experts Canada and Australia who have developed new techniques which allow the airways to be seen so that these changes can be measured.Read moreRead less
The Central Role Of Connective Tissue Growth Factor In Remodelling Of Asthmatic Airways
Funder
National Health and Medical Research Council
Funding Amount
$689,019.00
Summary
In the asthmatic airway an increase in the number of blood vessels can affect an asthmatic's ability to breathe. We have recently found that growth factors which can promote vessel growth are increased in the airways of asthmatics. We want to understand how these growth factors act together to possibly control the blood vessels and how their behaviour is different in the asthmatic airways compared to the nonasthmatic airways.
In the asthmatic lung structural changes, such as increased deposition of proteins which form the scaffolding of the airways (the extracellular matrix proteins), and an increased mass of bronchial smooth muscle cells occur. Many of these critical structural changes are not reversed or prevented with current asthma therapy, thus we need to investigate, by using lung cells and tissues , why they happen and how we can prevent them.
Urokinase Is A Key Mediator Of Airway Inflammation And Tissue Remodelling In Asthma
Funder
National Health and Medical Research Council
Funding Amount
$556,425.00
Summary
The scarring of airway tissue in asthma increases the difficulty of breathing. There is no effective treatment for airway scarring in severe asthma. This study looks at how proteins involved in dissolving blood clots influence wound healing and scarring in the airways. A better understanding of airway tissue scarring will lead to possible treatments for more serious forms of asthma which remain a major health and economic burden to our community.
MKP-1 As A Novel Anti-inflammatory Strategy In Asthma And Airway Remodelling
Funder
National Health and Medical Research Council
Funding Amount
$461,528.00
Summary
Asthma is a chronic disorder where airways are remodelled, or thickened, resulting in poor lung function. Airway remodelling is a consequence of long-term inflammation after multiple episodes of asthma. As the current drugs to treat remodelling have side effects, the aim of this grant is to investigate a novel anti-inflammatory strategy to reverse the development of airway remodelling by increasing the anti-inflammatory protein - MKP-1.